Vaglietti Serena, Villeri Veronica, Dell'Oca Marco, Marchetti Chiara, Cesano Federico, Rizzo Francesca, Miller Dave, LaPierre Louis, Pelassa Ilaria, Monje Francisco J, Colnaghi Luca, Ghirardi Mirella, Fiumara Ferdinando
Rita Levi Montalcini Department of Neuroscience, University of Turin, 10125 Turin, Italy.
Department of Chemistry, University of Turin, 10125 Turin, Italy.
iScience. 2023 Sep 27;26(10):108036. doi: 10.1016/j.isci.2023.108036. eCollection 2023 Oct 20.
The transcription factor FOXP2, a regulator of vocalization- and speech/language-related phenotypes, contains two long polyQ repeats (Q and Q) displaying marked, still enigmatic length variation across mammals. We found that the Q/Q length ratio quantitatively encodes vocalization frequency ranges, from the infrasonic to the ultrasonic, displaying striking convergent evolution patterns. Thus, species emitting ultrasonic vocalizations converge with bats in having a low ratio, whereas species vocalizing in the low-frequency/infrasonic range converge with elephants and whales, which have higher ratios. Similar, taxon-specific patterns were observed for the FOXP2-related protein FOXP1. At the molecular level, we observed that the FOXP2 polyQ tracts form coiled coils, assembling into condensates and fibrils, and drive liquid-liquid phase separation (LLPS). By integrating evolutionary and molecular analyses, we found that polyQ length variation related to vocalization frequency impacts FOXP2 structure, LLPS, and transcriptional activity, thus defining a novel form of polyQ length-based molecular encoding of vocalization frequency.
转录因子FOXP2是发声及言语/语言相关表型的调节因子，它包含两个长的多聚谷氨酰胺重复序列（Q和Q），在哺乳动物中显示出显著但仍不明的长度变异。我们发现，Q/Q长度比定量编码了从次声到超声的发声频率范围，呈现出惊人的趋同进化模式。因此，发出超声发声的物种与蝙蝠一样，具有较低的比值，而在低频/次声范围内发声的物种与大象和鲸鱼趋同，它们具有较高的比值。对于与FOXP2相关的蛋白FOXP1，也观察到了类似的、特定分类群的模式。在分子水平上，我们观察到FOXP2多聚谷氨酰胺序列形成卷曲螺旋，组装成凝聚物和原纤维，并驱动液-液相分离（LLPS）。通过整合进化分析和分子分析，我们发现与发声频率相关的多聚谷氨酰胺长度变异会影响FOXP2的结构、LLPS和转录活性，从而定义了一种基于多聚谷氨酰胺长度的发声频率分子编码新形式。
